Pollen has long been recognized as a cause of allergic rhinitis commonly called "hay fever". Pollen contains proteases which induce the release of mediators from mast cells stimulates IgE brosynthesis. The degranulation of mast cells by IgE results in the release of histamines which leads to an inflammatory response which causes congestion, itching swelling of sinuses. Many eosinophils are present in allergic patients with nasal mucus and neutrophils are present in patients with infected muscus.
Antihistamines are drugs commonly utilized which are taken orally that have a sedative effect. Alternatively, nasal sprays of the antihistamines can be utilized. However, such sprays have not been found to be long lasting and effective during the pollen season. Nasal sprays containing cromolyn sodium have been effective since cromolyn acts by blocking the reaction of allergen with tissue mast cells. However, cromolyn is not entirely effective since it apparently does not bind with some of the mediators of inflammation or the activators of IgE biosynthesis that stimulate the degranulation of mast cells and the production of histamines from the mast cells.
Inflammation is a non-specific response of tissues to diverse stimuli or insults and results in release of a variety of materials at the site of inflammation that induce pain. It is now recognized that mast cells, neutrophils and T-cells are implicated in the pathophysiology of inflammatory skin conditions as well as in other physiological disorders. Mast cells provide the greatest source of histamines in acute inflammation, as well as chymases, after degranulation by IgE. Serine protease inhibitors such as .alpha..sub.1 -antitrypsin and .alpha..sub.1 -antichymotrypsin have been found to be useful in the treatment of dermatitis by inhibiting and/or binding with elastase, cathepsin G and human mast cell chymase.
Alpha 1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver. It is a single glycopeptide chain of approximately 68,000 daltons and belongs to a class of serine protease inhibitors with an apparent affinity toward chymotrypsin-like enzymes. Alpha 1-antichymotrypsin is structurally related to alpha 1-antitrypsin.
Alpha 2-macroglobulin is a glycoprotein containing 8-11% carbohydrate which can be isolated from plasma by gel filtration chromatography.
Alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is a glycoprotein having a molecular weight of 53,000 determined by sedimentation equilibrium centrifugation. The glycoprotein consists of a single polypeptide chain to which several oligosaccharide units are covalently bonded. Human alpha 1-proteinase inhibitor has a role in controlling tissue destruction by endogenous serine proteinases. A genetic deficiency of alpha-1-proteinase inhibitor, which accounts for 90% of the trypsin inhibitory capacity in blood plasma, has been shown to be associated with the development of asthma and pulmonary emphysema. The degradation of elastin associated with certain inflammatory diseases probably results from a local imbalance of elastolytic enzymes and the naturally occurring tissue and plasma proteinase inhibitors. Alpha-1-proteinase inhibitor inhibits human pancreatic and leukocyte elastases. See Pannell et al, Biochemistry. 13, 5339 (1974); Johnson et al, Biochem. Biophys. Res. Commun., 72 33 (1976); Del Mar et al, Biochem. Biophys. Res. Commun., 88, 346 (1979); and Heimburger et al, Proc. Int. Res. Conf. Proteinase Inhibitors. 1st, 1-21 (1970).
The article of Groutas entitled "Inhibitors of Leukocyte Elastase and Leukocyte Cathepsin G Agents for the Treatment of Emphysema and Related Ailments" Medical Research Reviews, Vol. 7, No. 7, 227-241 (1987), discloses the role of eglin, elastinal 1 and elastin in emphysema.
U.S. Pat. No. 4,916,117 to Lezdey et al discloses the treatment of pulmonary inflammation where mast cells are involved with microcrystalline alpha-1-antichymotrypsin alone or with other serine protease inhibitors.
U.S. Pat. No. 4,732,973 to Barr et al, herein incorporated by reference which discloses active site modified protease .alpha.-1-antitrypsin inhibitors which can be used in the present invention.
It is understood that the term "serine protease inhibitors" as used herein is meant to include the analogs, derivatives or salts, which are derived naturally or by recombinant technology.